A Caspase-Independent Pathway of MHC Class II Antigen-Mediated Apoptosis of Human B Lymphocytes

摘要: MHC class II molecules have a crucial role in thymic selection and generating Ag-specific T cell responses. There is extensive evidence for second messenger generation via molecules, which can lead to apoptosis of B lymphocytes. We examined HLA II-mediated both normal tumoral human Phosphatidylserine exposure DNA fragmentation were observed cells within 24 h stimulation II. In marked comparison with Fas, the cell-permeable irreversible caspase inhibitors zVAD-fmk DEVD-fmk failed inhibit HLA-DR-mediated apoptosis. No direct activation 3 was detected, cleavage pro-caspase not observed. Cleavage poly(ADP-ribose) polymerase detected Fas but Although phosphatidylinositol-3-kinase has been implicated I-mediated apoptosis, neither wortmannin nor LY294002 affected CD95-sensitive used reveal that death occurred independently CD95-CD95 ligand interactions. Overall, these data pathway requires involves caspases. Moreover, it independent Fas/CD95 independent. This could an important regulation APC populations or control malignant lymphocyte proliferations.